To assess the effect of recombinant human erythropoietin (EPO) on renal function, the slopes of the regression lines of the reciprocal of serum Cr versus month (l/Cr) were studied in 8 pre-dialysis outpatients (2.9 ml/min. less than Ccr less than 17.0, 21.4% less than Ht less than 27.9) who had been followed for a period of 19 to 94 months. EPO was initially given 3000-6000 U (133 +/- 31 U/Kg/week) once weekly by the intravenous route and was later switched to the dose to achieve a Ht level of 30-35%. Mean Ht increased from 23.6 +/- 0.9 to 33.2 +/- 1.1%, and quality of life and exercise capacity were significantly improved in all patients. The mean slopes of l/Cr after EPO (-0.0050 +/- 0.0020) were not significantly different from the values before EPO (-0.0064 +/- 0.0010). The slopes of l/Cr were significantly decreased by EPO therapy in three patients observed for more than 17 months, however in one patient, it increased significantly during EPO treatment. There were no significant differences in the other 4 patients. The renal function at the initiation of EPO in a patient with increase slope of l/Cr had been the worst, and Ht was mildly increased from 21.4% to 24.1% and the blood pressure did not change significantly. The good effect on renal function observed in 3 patients may, in part, be due to better control of blood pressure and physical condition (including cardiac and immunological function) by the more close follow-up of the patients and the improvement of anemia during the period of EPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)